Alterations in gastrointestinal microbiota related to diet and common use of antibiotics are strongly associated with allergies and asthma. Probiotics (those microbes that produce only beneficial effects in the host gut), such as Lactobacillus and Bifidobacterium are reduced in the intestinal microbiota of atopic individuals and westernized populations. These probiotics have shown beneficial effects in the prevention and treatment of atopic disease, through improved intestinal barrier function and immunomodulation. One disease particularly in need of effective alternative therapy is asthma, which, along with other atopic diseases, is on the rise in the United States. Asthma results from deficient Treg responses leading to inappropriate TH2 cell-mediated immune response to common allergens, and several investigators have suggested that alteration of GI mucosal barrier function may be relevant to asthma pathogenesis. Traditional therapies focused on topical delivery to the lung to control inflammation have been insufficient perhaps because the intestinal mucosal barrier is dysfunctional. One multiorganism probiotic, VSL#3 contains 8 lactic acid bacteria, including Bifidobacterium and Lactobacillus species, which have synergistic properties for establishing stability of immunotolerant microbiota in chronic gastrointestinal disorders, restoring the gut barrier, and enhancing T cell regulatory function. Establishing a more favorable microbial balance in asthmatics could lead to a new strategy that will help control this and other chronic diseases affected by impaired GI mucosal function. Because the use of VSL#3 in asthma is novel, the FDA requires that we conduct an open label safety study of VSL#3 in this potentially vulnerable population before a placebo controlled trial; in the course of this Phase I safety study, mechanistic data regarding the health effects of VSL#3 can be acquired. [unreadable] Our overall goal is to restore mucosal barrier integrity in chronic diseases, with the expectation that this will lead to diminished clinical severity. The objective of this study is to evaluate the safety and efficacy of probiotic therapies in this regard, focusing on asthmatics, who have increased intestinal permeability and a TH2 allergic response to inhaled and ingested particles. HYPOTHESIS: The multiorganism probiotic, VSL#3, is safe and effective in asthmatics by improving intestinal barrier function and diverting the immune system to a more regulatory or tolerant state. Aim 1: To establish safety and potential efficacy of the commercially available probiotic, VSL#3, in asthmatics. Measurable safety outcomes before during and after twice daily consumption of VSL#3 for 3 months will include frequency of unscheduled asthma-related health care visits; number of days with asthma symptoms; frequency of asthma related work/school days missed; use of asthma rescue medications; and pulmonary function. We hypothesize that VSL#3 will be well tolerated. Aim 2: To test the ability of VSL#3 to enhance intestinal barrier function in asthmatics. We will measure intestinal permeability in this cohort to identify potential mechanisms to explain safety concerns and/or potential clinical benefit to subjects whose asthma control is measured in Aim 1 of this safety trial. We hypothesize that VSL#3 will be established in the GI tract, and will lead to improved intestinal barrier function in asthmatics in this safety trial. We will confirm that VSL#3 is viable in the GI tract of study participants to confirm adherence to therapy. Viability of the organism will be detected by stool collection and VSL#3 species identified by culture and real time PCR. Aim 3: To determine that VSL#3 in asthmatic subjects leads to immune tolerance. We will gather data on immune cell subsets using FACS analysis and spontaneous and activated peripheral blood mononuclear cell (PBMC) cytokine profiles of this cohort to identify potential mechanisms to explain safety concerns and/or potential clinical benefit to subjects whose asthma control is measured in Aim 1. Based on studies in other cohorts consuming VSL#3, we expect that VSL#3 will divert the immune system to a regulatory or tolerant mode with increased IL-10 production and downregulation of TH-2 cytokines IL- 4, IL-5, and IL-13. [unreadable] [unreadable] [unreadable]